{"created":"2023-05-15T09:41:11.301894+00:00","id":231,"links":{},"metadata":{"_buckets":{"deposit":"a4f3e375-7961-415e-8cb6-ac82a73bfcda"},"_deposit":{"created_by":11,"id":"231","owners":[11],"pid":{"revision_id":0,"type":"depid","value":"231"},"status":"published"},"_oai":{"id":"oai:kagawa-u.repo.nii.ac.jp:00000231","sets":["13:40"]},"author_link":["1542"],"item_10006_date_granted_11":{"attribute_name":"学位授与年月日","attribute_value_mlt":[{"subitem_dategranted":"2014-12-24"}]},"item_10006_degree_grantor_9":{"attribute_name":"学位授与機関","attribute_value_mlt":[{"subitem_degreegrantor":[{"subitem_degreegrantor_language":"ja","subitem_degreegrantor_name":"香川大学"},{"subitem_degreegrantor_language":"en","subitem_degreegrantor_name":"Kagawa University"}],"subitem_degreegrantor_identifier":[{"subitem_degreegrantor_identifier_name":"16201","subitem_degreegrantor_identifier_scheme":"kakenhi"}]}]},"item_10006_degree_name_8":{"attribute_name":"学位名","attribute_value_mlt":[{"subitem_degreename":"博士（医学）","subitem_degreename_language":"ja"}]},"item_10006_description_7":{"attribute_name":"抄録","attribute_value_mlt":[{"subitem_description":"Abstract\nWe examined the biological functions of the gene Cbl in erythropoietin (EPO) signaling using Cbl-deficient F-36P human erythroleukemia cells by the introduction of the Cbl siRNA expression vector. Knockdown of Cbl promoted EPO-dependent proliferation and survival of F-36P cells, especially at a low concentration of EPO (0.01 U/mL), similar to serum concentrations of EPO in healthy volunteers (0.005–0.04 U/mL). We found that Src was degraded mainly by the proteasomal pathway because the proteasome inhibitor MG-132 but not the lysosome inhibitor NH4Cl suppressed the EPO-induced degradation of Src in F-36P cells and that knockdown of Cbl inhibited EPO-induced ubiquitination and degradation of Src in F-36P cells. The experiments using the Src inhibitor PP1 and co-expression experiments further confirmed that Cbl and the kinase activity of Src are required for the EPO-induced ubiquitination of Src. In addition, the co-expression experiments and in vitro kinase assay demonstrated that the EPO-induced tyrosine phosphorylation and ubiquitination of Cbl were dependent on the kinase activity of Src but not Jak2. Thus, Cbl negatively regulates EPO signaling mainly through the proteasome-dependent degradation of Src, and the E3 ligase activity of Cbl and its tyrosine phosphorylation are regulated by Src but not Jak2.","subitem_description_language":"en","subitem_description_type":"Abstract"}]},"item_10006_dissertation_number_12":{"attribute_name":"学位授与番号","attribute_value_mlt":[{"subitem_dissertationnumber":"甲第599号"}]},"item_10006_relation_15":{"attribute_name":"関連サイト","attribute_value_mlt":[{"subitem_relation_type":"isVersionOf","subitem_relation_type_id":{"subitem_relation_type_id_text":"https://doi.org/10.1016/j.bcmd.2014.06.005","subitem_relation_type_select":"DOI"}},{"subitem_relation_type":"isIdenticalTo","subitem_relation_type_id":{"subitem_relation_type_id_text":"https://dl.ndl.go.jp/pid/10224392","subitem_relation_type_select":"URI"}}]},"item_10006_relation_22":{"attribute_name":"PubMed番号","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"25084697","subitem_relation_type_select":"PMID"}}]},"item_10006_relation_28":{"attribute_name":"論文ID（NAID）","attribute_value_mlt":[{"subitem_relation_type_id":{"subitem_relation_type_id_text":"500000993693","subitem_relation_type_select":"NAID"}}]},"item_10006_rights_13":{"attribute_name":"権利","attribute_value_mlt":[{"subitem_rights":"Copyright © 2014 Elsevier Inc. All rights reserved.","subitem_rights_language":"en"}]},"item_10006_text_30":{"attribute_name":"KEID","attribute_value_mlt":[{"subitem_text_value":"27638"}]},"item_10006_version_type_18":{"attribute_name":"著者版フラグ","attribute_value_mlt":[{"subitem_version_resource":"http://purl.org/coar/version/c_fa2ee174bc00049f","subitem_version_type":"P"}]},"item_access_right":{"attribute_name":"アクセス権","attribute_value_mlt":[{"subitem_access_right":"open access","subitem_access_right_uri":"http://purl.org/coar/access_right/c_abf2"}]},"item_creator":{"attribute_name":"著者","attribute_type":"creator","attribute_value_mlt":[{"creatorAffiliations":[{"affiliationNameIdentifiers":[{"affiliationNameIdentifier":""}],"affiliationNames":[{"affiliationName":""}]}],"creatorNames":[{"creatorName":"Shintani, Takamichi","creatorNameLang":"en"},{"creatorName":"新谷, 高理","creatorNameLang":"ja"},{"creatorName":"シンタニ, タカミチ","creatorNameLang":"ja-Kana"}],"familyNames":[{},{},{}],"givenNames":[{},{},{}],"nameIdentifiers":[{},{}]}]},"item_files":{"attribute_name":"ファイル情報","attribute_type":"file","attribute_value_mlt":[{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2020-10-27"}],"displaytype":"detail","filename":"Med_A599.pdf","filesize":[{"value":"3.5 MB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"本文","objectType":"fulltext","url":"https://kagawa-u.repo.nii.ac.jp/record/231/files/Med_A599.pdf"},"version_id":"b19e0c51-e345-40f7-87ce-ab66b0ab23e6"},{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2020-10-27"}],"displaytype":"detail","filename":"Med_A599_abstract.pdf","filesize":[{"value":"266.1 kB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"内容の要旨","objectType":"abstract","url":"https://kagawa-u.repo.nii.ac.jp/record/231/files/Med_A599_abstract.pdf"},"version_id":"91bcab2d-4287-4ada-a3e5-1578e58e6992"},{"accessrole":"open_date","date":[{"dateType":"Available","dateValue":"2020-10-27"}],"displaytype":"detail","filename":"Med_A599_result.pdf","filesize":[{"value":"257.3 kB"}],"format":"application/pdf","licensetype":"license_note","mimetype":"application/pdf","url":{"label":"審査の結果の要旨","objectType":"other","url":"https://kagawa-u.repo.nii.ac.jp/record/231/files/Med_A599_result.pdf"},"version_id":"4eea26b4-153b-438e-a47d-401cf74a5704"}]},"item_keyword":{"attribute_name":"キーワード","attribute_value_mlt":[{"subitem_subject":"Cbl","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Erythropoietin","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Proteasome","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Src","subitem_subject_language":"en","subitem_subject_scheme":"Other"},{"subitem_subject":"Ubiquitination","subitem_subject_language":"en","subitem_subject_scheme":"Other"}]},"item_language":{"attribute_name":"言語","attribute_value_mlt":[{"subitem_language":"eng"}]},"item_resource_type":{"attribute_name":"資源タイプ","attribute_value_mlt":[{"resourcetype":"doctoral thesis","resourceuri":"http://purl.org/coar/resource_type/c_db06"}]},"item_title":"Cbl negatively regulates erythropoietin-induced growth and survival signaling through the proteasomal degradation of Src kinase","item_titles":{"attribute_name":"タイトル","attribute_value_mlt":[{"subitem_title":"Cbl negatively regulates erythropoietin-induced growth and survival signaling through the proteasomal degradation of Src kinase","subitem_title_language":"en"}]},"item_type_id":"10006","owner":"11","path":["40"],"pubdate":{"attribute_name":"PubDate","attribute_value":"2014-12-24"},"publish_date":"2014-12-24","publish_status":"0","recid":"231","relation_version_is_last":true,"title":["Cbl negatively regulates erythropoietin-induced growth and survival signaling through the proteasomal degradation of Src kinase"],"weko_creator_id":"11","weko_shared_id":-1},"updated":"2024-02-06T08:56:51.582969+00:00"}